A novel concept in enteric coating: a double-coating system providing rapid drug release in the proximal small intestine.
A novel double-coating enteric system was developed to accelerate drug release in conditions resembling the upper small intestine. The system comprises an inner coat (partially neutralised EUDRAGIT L 30 D-55 and organic acid) and an outer coat (standard EUDRAGIT L 30 D-55). Prednisolone tablets were coated with double layer formulations with inner coats neutralised to pH 5.6 in the presence of 10% citric acid or adipic acid. A conventional single coating was also applied for comparison purposes. There was no drug release from the single coated or double-coated tablets in 0.1M HCl for 2 h using USP II apparatus. The lag times of drug release in subsequent pH 5.6 phosphate buffer (to resemble the pH condition of the proximal small intestine) were 102, 42 and 28 min for the single coated, adipic acid and citric acid double-coated tablets respectively. The lag time for release from the double-coated tablets was further reduced to 5 min when the inner coat was neutralised to pH 6.0 in the presence of 10% citric acid. The rapid drug release from the double-coating system was associated with faster polymer dissolution rates compared to the single coating. The novel double-coated system has the potential to provide rapid drug release in the proximal small intestine, overcoming the limitations of conventional enteric coatings.
Liu
Fang
F
Department of Pharmaceutics, The School of Pharmacy, University of London, London, United Kingdom.
Lizio
Rosario
R
Meier
Christian
C
Petereit
Hans-Ulrich
HU
Blakey
Peter
P
Basit
Abdul W
AW
D000272:Adipates / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002951:Citrates / Q000737:chemistry; D019343:Citric Acid / Q000737:chemistry; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism*; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009994:Osmolar Concentration; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D011239:Prednisolone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013499:Surface Properties; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D000272:Adipates; D000893:Anti-Inflammatory Agents; D002951:Citrates; C477852:Eudragit L 30 D-55; D008689:Methacrylates; D004364:Pharmaceutical Preparations; D011108:Polymers; D013608:Tablets, Enteric-Coated; D019343:Citric Acid; C029900:adipic acid; C023001:ethyl citrate; D011239:Prednisolone